Right ventricular pressure overload alters cardiac lipid composition.

Area of Science:

• Cardiovascular Physiology
• Metabolic Regulation
• Cardiac Remodeling

Background:

• Right ventricular (RV) failure is a critical factor in pulmonary hypertension, congenital heart disease, and left ventricular failure.
• Metabolic dysregulation is increasingly recognized as a contributor to RV failure, though underlying mechanisms require further elucidation.
• Disruption of intracardiac lipid content is a recently proposed factor in RV failure development.

Purpose of the Study:

• To investigate temporal changes in RV function, remodeling, and metabolism in a rat model of RV dysfunction.
• To correlate these changes with alterations in RV lipid content under pressure load.

Main Methods:

• A rat model of pulmonary artery banding was used to induce RV pressure overload.
• Hemodynamic, cellular, and metabolic assessments were performed at 2, 5, and 12 weeks post-intervention.
• Lipidomics analysis was employed to quantify changes in myocardial lipid species.

Main Results:

• Pulmonary artery banding induced RV dysfunction and remodeling, with early upregulation of oxidative stress markers.
• Significant decreases in myocardial diglycerides and cardiolipins, particularly unsaturated forms like tetralinoleoylcardiolipin, were observed after 12 weeks.
• Mitochondrial capacity for fatty acid oxidation remained preserved, while glucose oxidation capacity increased.

Conclusions:

• RV dysfunction from pressure overload is associated with reduced intracardiac unsaturated lipids, notably tetralinoleoylcardiolipin.
• This lipid reduction coincided with preserved fatty acid oxidation but increased glucose oxidation and early oxidative stress.
• Early interventions targeting lipid availability may be a strategy to prevent RV failure.